Hemolytic Anemia: Immune Anemias - PowerPoint Presentation

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Hemolytic Anemia: Immune Anemias

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Learning Objectives—Level IAt the end of this unit of study, the student should be able to:List the antibody systems or specificities usually involved in:cold agglutinin syndromeparoxysmal cold hemoglobinuria (PCH)warm autoimmune hemolytic anemias (WAIHA)

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Learning Objectives—Level IAt the end of this unit of study, the student should be able to:Describe the purpose and general procedure for the direct antiglobulin test (DAT), and identify the typical DAT profile (polyspecific AHG, anti-IgG, anti-C3) found in patients with cold agglutinin syndrome and warm autoimmune hemolytic anemia.

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Learning Objectives—Level IAt the end of this unit of study, the student should be able to:Describe and recognize the characteristic hematologic findings associated with the following conditions:cold agglutinin syndromewarm autoimmune hemolytic anemia (WAIHA)

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Learning Objectives—Level IAt the end of this unit of study, the student should be able to:Describe and recognize the typical hematologic laboratory findings in ABO and Rh hemolytic disease of the fetus and newborn (HDFN).

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Learning Objectives—Level IAt the end of this unit of study, the student should be able to:Contrast alloimmune and autoimmune hemolytic anemias including stimulus for antibody production, site of hemolysis, type of antibody involved, and direct antiglobulin test (DAT) and indirect antiglobulin test (IAT) reactions.

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Learning Objectives—Level IIAt the end of this unit of study, the student should be able to:Compare the pathophysiology of extravascular and intravascular hemolysis in immune hemolytic anemia (IHA) including site of destruction, immunoglobulin class of antibody, and underlying mechanism.

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Learning Objectives—Level IIAt the end of this unit of study, the student should be able to:Given a set of laboratory data, determine the underlying mechanism of hemolysis and suggest confirmatory tests.

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Learning Objectives—Level IIAt the end of this unit of study, the student should be able to:Contrast the different mechanisms of drug-induced immune hemolytic anemia and tests commonly used for confirmation, and identify the drugs commonly involved.Describe the mechanism of hemolysis, select the confirmatory tests for paroxysmal cold hemoglobinuria (PCH), and evaluate the results.

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Learning Objectives—Level IIAt the end of this unit of study, the student should be able to:Compare the prenatal and postnatal pathophysiology of hemolytic disease of the newborn (HDFN).Interpret the results of laboratory tests for HDFN, and determine whether evidence of hemolysis is present.

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IntroductionImmune hemolytic anemia (IHA)RBCs destroyed prematurely by immune process mediated by antibody and/or complementPresence and severity of anemia depends on:Severity of hemolysisAbility of BM to compensate for RBC loss

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IntroductionImmune hemolytic anemia (IHA)Initial confirmation of immune mechanismDemonstration of attachment of Ab or complement to RBCs of patientDiagnosis of anemia: ↓ Hb and Hct, ↑ reticulocytes and/or unconjugated bilirubin, ↓ haptoglobin

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Classification of IHAsBased on stimulus for antibody productionAutoimmune hemolytic anemiaDrug-induced hemolytic anemiaAlloimmune hemolytic anemiaImportant to determine process because each type requires specific treatment

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ClassificationAutoimmune hemolytic anemia (AIHA)Shortened RBC survivalCaused by production of autoantibodies against RBC antigensAb-induced reactions includeSensitization, agglutination, hemolysis

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ClassificationAutoimmune hemolytic anemia (AIHA)Further classifiedWarm-antibody autoimmune HA (WAIHA)Cold-antibody AIHA (cold agglutinin disease/CAD)Mixed-type AIHA (both warm-reacting and cold-reacting autoantibodies)

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Table 19-1 Classification of Immune Hemolytic Anemias

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Table 19-2 Characteristics of Agglutinins in Hemolytic Anemia

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ClassificationDrug-induced hemolytic anemiaDrugs attach to RBC membrane or alter it.Classified based on reactions of patient's RBCs and drug in vitro test systemDrug-dependentDrug-independent

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ClassificationAlloimmune hemolytic anemiaAntibody (Ab) development to RBC antigen (Ag) that individual lacksDo not react with individual's own RBCsHDFN-mother makes Abs against Ags on fetal RBCsTransfusion reactions where recipient makes Abs to Ags on transfused (donor cells)

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Sites and Factors that Affect HemolysisIntravascular or extravascular hemolysisDepends on:Class of AbAbility to fully activate complement cascade

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Sites and Factors that Affect HemolysisIntravascular or extravascular hemolysisExtravascular hemolysisMost common RBC sensitized with Ab or complementSensitized cells phagocytized by macrophages in spleen or liver

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Sites and Factors that Affect HemolysisIntravascular or extravascular hemolysisIntravascular hemolysisComplement cascade activated → C9 (MAC) → RBC lysis

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Figure 19-1 Immune-mediated extravascular hemolysis. Erythrocytes sensitized with antibody or complement (C3b) attach to macrophages via specific cell receptors for these immune proteins.

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Table 19-3 Factors Affecting the Rate of Hemolysis in Immune Hemolytic Anemias

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Mechanisms of HemolysisBased on whether IgM, IgG, and/or complement are present on RBCThree types:IgG-mediatedComplement-mediatedIgM-mediated

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IgG-Mediated HemolysisIgG attaches to RBC membrane Ags via Fab region.Fc receptorsFcγR-I, -II, -III on macrophages of spleen Bind to Fc portion of Ab attached to RBCMacrophage pits the Ag/Ab complex

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IgG-Mediated HemolysisFc receptorsDamages RBC membraneRBC membrane reseals itselfRepeated splenic passage—continues to lose membrane, forms spherocytePhagocytized by splenic macrophages

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IgG-Mediated HemolysisAb-sensitized RBCs can be entirely engulfed by: MacrophagesPMN (FcγR-I, -III) NK cells (FcγR-III)—results in ADCC (Ab dependent cell-mediated cytotoxicity)

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IgG-Mediated HemolysisSpleenLightly opsonized cells more efficiently removedLiverRemoves heavily sensitized cellsSplenomegaly is common

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Complement-Mediated HemolysisRole of complement Sensitization Only portion of complement cascade activated and deposited on RBC membraneLysis of RBCsEntire complement system activated and deposited on RBC membrane

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Complement-Mediated HemolysisInitiation of complement activation Classic, alternate, lectin mechanismsClassic pathwayInitiated by Ag/Ab reactionIgM Activates complement more efficientlyOnly requires one IgM moleculeIgG (IgG1 and IgG3; occasional IgG2)Activation requires two IgG molecules

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Complement-Mediated HemolysisCascade initiatedC1 binds to the Fc region of IgG or IgM.Activates C4, C2, C3Activates the terminal components C5 to C9Membrane attack complex (MAC)Lytic attack to RBC membraneIntravascular hemolysis when complement activation C1→C9 is complete

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Complement-Mediated HemolysisCascade initiatedActivations through C3RBC sensitized with C3bTotally or partially engulfed by macrophages with receptors for C3bC3b on RBC cleaved by plasma C3b inactivator C3c dissociates from membrane.C3d no receptors on macrophagesNormal RBC survival

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Figure 19-2 The complement cascade. The central event in complement activation is the activation of C3 by C3 convertases. This can occur by two separate but interrelated mechanisms, the classic and alternate pathways. The classic complement pathway is initiated by an antigen–antibody reaction. The antigen–antibody complex activates the C1q, r, s complex, which in turn activates C4 by proteolytic cleavage to C4a and C4b. C2 binds to C4b and is proteolytically cleaved by C1s to form C2a and C2b. The C4b2a complex serves as C3 convertase. In the alternate pathway, C3b serves as the cofactor of the C3-cleaving enzyme complex (C3b, P, Bb), also known as C3 convertase. Thus, C3b serves to prime its own activation. The C3b formed through the classic pathway can directly initiate the assembly of the alternate pathway C3 convertase. C3 can also be activated by spontaneous hydrolysis. The C3b complexes formed by the classic and alternate pathways activate C5 to C5a and C5b. Membrane damage is initiated by the assembly of C5b with C6, 7, 8, 9.

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IgM-Mediated HemolysisMacrophages do not have receptors for Fc portion of IgM. IgM is efficient activator of complement IntravascularComplement activation through C9 and RBC hemolyzes

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IgM-Mediated HemolysisMacrophages do not have receptors for Fc portion of IgM. IgM is efficient activator of complement.Extravascular Activation incompleteC3b coats RBCs and sensitized cells destroyed extravascularly via CR1 and CR3 receptors on macrophages.IgM can agglutinate cells in addition to activating complement.

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Laboratory ID of Sensitized RBCsTwo agglutination techniquesSaline—detects IgM antibodiesAHG test—detects IgG and/or complementDirect AHG (DAT)Detects RBCs coated in vivoRequired to differentiate AIHA from other types of HA

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Laboratory ID of Sensitized RBCsTwo agglutination techniquesAHG test—detects IgG and/or complementIndirect AHG (IAT)Detects antigens in plasma or serum (in vitro)Indicates alloimmunization or free autoAbs in patient's serum

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Figure 19-3 The zeta potential of erythrocytes keeps the cells about 25 nm apart when suspended in saline. IgG antibodies have a span of about 14 nm, not enough to bridge the gap between cells and cause agglutination. IgM antibodies, however, are pentamers with a span of about 35 nm, a distance sufficient to bridge the space between cells and cause agglutination.

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Laboratory ID of Sensitized RBCsNegative DAT in AIHACan result fromInsufficient number IgG molecules on RBCsAutoantibodies of IgA or IgM classAutoantibodies with low affinity for RBCs

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Laboratory ID of Sensitized RBCsNegative DAT in AIHANewer techniques more sensitiveEnzyme linked DATGel testsFlow cytometryPolybrene tests

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Laboratory ID of Sensitized RBCsPositive DAT in normal individualHealthy blood donors and hospitalized patients Positive DAT—No shortened RBC survival

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Laboratory ID of Sensitized RBCsPositive DAT in normal individualPossible causes:Inefficient macrophage removal of sensitized RBCsInsufficient quantity of Ab on cell surfaceSubclass of Ab not recognized by macrophage

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Laboratory ID of Sensitized RBCsPositive DAT in normal individualPossible causes:Thermal amplitude of antibody (< 37°C)+ DAT due to presence of complement on RBCsPatients with hypergammaglobulinemia or receiving high-dose IV gamma globulin exhibit nonspecific binding.

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Autoimmune Hemolytic Anemias (AIHA)

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AIHAImmune tolerance normally prevents formation of autoantibodiesAutoimmune diseases occur because:Genetic predispositionExposure to infectious agents (molecular mimicry)Defects in regulation of immune tolerance

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AIHAImmune tolerance normally prevents formation of autoantibodiesSubcategoriesWarm vs cold autoantibodiesFurther categorized asPrimary vs secondary AIHA

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Warm AIHAAccounts for ~ 70% of cases AIHAOptimal reactivity at 37°CUsually IgG (rarely IgM, IgA)Most Abs react with "Rh protein" complexDo not react with Rh null or Rh deleted cellsOccasionally have single specificity within Rh system (e.g., anti-e)

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Warm AIHAAccounts for ~ 70% of cases AIHAMost hemolysis is extravascular via splenic macrophages.

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Warm AIHAIdiopathic WAIHA Accounts for about 60% of cases of warm AIHAAcute idiopathic WAIHASevere anemia Developing over two to three daysHemolysis is self limited Several weeks → several years duration

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Warm AIHAIdiopathic WAIHA Chronic idiopathic WAIHSHemolysis is unabating.

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Warm AIHASecondary WAIHA associated with:Lymphoproliferative disease CLL, HDNeoplastic diseasesAutoimmune disorders SLE, RA, Crohn's disease, and so onCertain viral and bacterial infectionsVaccines

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Warm AIHAClinical findingsCan occur at any age Incidence ↑ after age 40Common presentationSymptoms of anemia

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Warm AIHAClinical findingsSecondary AIHASigns and symptoms of underlying disorderMild to moderate splenomegaly > 50% patients, hepatomegaly in ⅓ patients

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Warm AIHALaboratory findingsImmune-mediated hemolysis+ DATAutoantibody in the serumPresence of spherocytes

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Warm AIHALaboratory findingsPeripheral bloodModerate to severe normocytic/normochromic anemiaReticulocytosisPolychromasia, NRBCs, spherocytes, schistocytes

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Figure 19-4 BA blood smear from a patient with warm autoimmune hemolytic anemia (WAIHA). The marked anisocytosis is due to the presence of spherocytes and large polychromatophilic erythrocytes. The nucleated cells are erythroblasts (Wright stain, 1000× original magnification).

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Warm AIHALaboratory findingsBone marrowErythroid hyperplasia, erythrophagocytosisOther lab tests+ DAT+ polyspecific AHG and anti-IgG monospecific AHG30% + anti-C3

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Warm AIHALaboratory findingsDifferential diagnosis from HS+ DAT Autohemolysis test not corrected by glucoseNon-homogeneous population of spherocytes

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Table 19-4 Laboratory Findings Associated with WAIHA

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Warm AIHATherapySelf-limited hemolytic disorders Do not require transfusions.Patients needing transfusionsDifficulty finding compatible donor cells

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Warm AIHATherapyOther therapiesImmunosuppressive drugs, cytotoxic drugsSplenectomyRituximabIVIG—high dose intravenous immunoglobulinPlasma exchange and plasmapheresis

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Cold AIHAAccounts for ~ 16–30% of cases of AIHAOptimal reactivity < 37°CUsually IgM, with complement activation Rarely IgA or IgGMost Abs react with I/i Ags or Pr Ags

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Cold AIHAAccounts for ~ 16–30% of cases of AIHASeverity of disease Related to thermal range of the AbMost hemolysis due to complement-mediated lysis

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Cold AIHAIdiopathic or secondary Idiopathic CAS (cold agglutinin syndrome)Usually chronic, occurring after age 50Ab involved is usually Monoclonal IgM/kappa with autoanti-I specificity

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Cold AIHAIdiopathic or secondarySecondary CASAssociated with infectious disease Usually acute, self-limitingPolyclonal autoAbs with specificity for Ii antigensanti-I—M. pneumoniaeanti-I—Infectious mononucleosisanti-Pr—varicella, rubella

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Cold AIHAIdiopathic or secondarySecondary CASAssociated with lymphoproliferative disorders Usually chronic, found in older individualsMonoclonal IgMκ Ab

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Table 19-5 Autoimmune Hemolytic Anemia Caused by Cold-Reacting Antibodies

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Cold AIHAClinical findingsChronic or episodic hemolytic anemiaRBC agglutination Areas of the body that cool to the Ab thermal rangeSludging of blood flow within capillaries

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Cold AIHAClinical findingsVascular changesAcrocyanosisRaynaud's phenomenonPain with color change patterns in skinHemoglobinuria and splenomegaly

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Cold AIHALaboratory findingsAutomated blood countsFalsely ↓ RBCFalsely ↑ MCVMust warm blood and diluting reagents

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Cold AIHALaboratory findingsMild to moderate anemiaNormocytic/normochromicPolychromasia, spherocytes, clumps of RBCs, NRBCs, erythrophagocytosisBone marrowNormoblastic hyperplasia

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Table 19-6 Criteria for Clinical Diagnosis of Cold Agglutinin Syndrome (CAS)

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Figure 19-5 Cold autoimmune hemolytic anemia from a patient with chronic lymphocytic leukemia. Some of the erythrocytes are in small clumps. Spherocytes are also present (peripheral blood, Wright stain, 1000 original magnification).

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Cold AIHALaboratory findingsDifferential diagnosisBenign cold autoagglutinins vs pathologic cold agglutininsPathologic cold agglutinins+ DAT for polyspecific AHG and monospecific anticomplement antiserumCold agglutinin test—agglutinates RBCs at 0–20°C in saline, reversible at 37°CTiter usually > 1:1000 (normal 1:64)

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Table 19-7 Comparison of Characteristics of Pathologic Cold Agglutinins Found in CAS with Those of Benign Cold Agglutinins Found in Normal Individuals

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Cold AIHATherapyKeeping extremities warm is most effectiveSecondary to lymphoproliferative disorderChemotherapyPlasma exchange for acute hemolytic episodesEffective for short time

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Paroxysmal Cold Hemoglobinuria (PCH)Rare autoimmune hemolytic disorder Can occur at any ageMassive intermittent acute hemolysis and hemoglobinuriaAccounts for 30–40% of all AIHA in children Most frequent < age 5Associated with viral and bacterial infections

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Paroxysmal Cold Hemoglobinuria (PCH)Rare autoimmune hemolytic disorder Usually transient disorderResolves spontaneouslyTransfusions may be needed in severe cases.

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Paroxysmal Cold Hemoglobinuria (PCH)PathophysiologyBi-phasic complement fixing IgG antibody Donath Landsteiner antibodyBinds RBCs at low temps (< 20°C), activates complement

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Paroxysmal Cold Hemoglobinuria (PCH)PathophysiologyBi-phasic complement fixing IgG antibody Upon warming to 37°Ab detaches RBC lysed by complement activation through C9 (MAC)Usual reactivity—autoanti-P antibody

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Paroxysmal Cold Hemoglobinuria (PCH)Clinical findingsHemoglobinuria most common clinical symptomJaundice, pallor, hepatosplenomegalyRaynaud's phenomenon can occur

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Paroxysmal Cold Hemoglobinuria (PCH)Laboratory findingsAnemia depends on frequency and severity of attack.Hb drops sharply—Can ↓ as low as 5 g/dL.Hemoglobinemia, methemalbuminemia, hemoglobinuria

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Paroxysmal Cold Hemoglobinuria (PCH)Laboratory findingsNeutropenia, neutrophil shift to leftReticulocytopenia, spherocytes↑ serum bilirubin, BUN, LD↓ serum complement, haptoglobinErythrophagocytosis

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Paroxysmal Cold Hemoglobinuria (PCH)Laboratory findingsDAT usually negative for antibodiesDAT weakly + for complementIAT + if performed in coldDonath-Landsteiner antibodiesPresent in low titers < 1:32Verified by D-L test

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Table 19-8 Donath-Landsteiner (D-L) Test for Detecting the Presence of D-L Antibodiesa

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Paroxysmal Cold Hemoglobinuria (PCH)TherapyPCH terminates with recovery from infection.Transfusion if hemolysis is severePlasmapheresis if hemolysis persistsRituximabAvoid exposure to cold

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Table 19-9 Comparison of Cold Agglutinin Syndrome (CAS) and Paroxysmal Cold Hemoglobinuria (PCH)

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Mixed-Type AIHADue to presence of warm-reacting IgG autoAb and cold-reacting IgM autoAb Both have high titer and ↑ thermal amplitude50% of cases are idiopathic.Remainder associated with lymphoproliferative diseases, autoimmune diseases (e.g., SLE), or HIV

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Mixed-Type AIHADue to presence of warm-reacting IgG autoAb and cold-reacting IgM autoAbMixture of both intravascular (IgM) and extravascular (IgG) hemolysisMost patients respond to corticosteroids without transfusions.

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Drug-Induced Hemolytic Anemias

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Drug-Induced HAAcquired cause of hemolytic anemiaNot all individuals taking the same drug develop HA.> 125 drugs identifiedImmune response to drug-induced alteration of RBCMust differentiate from:Drug-induced, nonimmune hemolysisSpontaneous autoimmune disorders

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Drug-Induced HAUncommon acquired cause of HAResolution is withdrawal of drug.Classic mechanismsDrug absorption, immune complex formation, autoantibody induction, membrane modificationNew "unifying" hypothesis

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Drug-Induced HAUncommon acquired cause of HANew "unified" hypothesisDrug binds to RBC membrane.Abs produced to react with epitopes specific to drugCombination of drug and RBC proteinsEpitopes primarily on RBC membraneExplains how patients develop more than one type of drug-induced Ab

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Drug-Induced HAUncommon acquired cause of HANew "unified" hypothesisTwo types:Drug dependent—requires presence of drug during testingDrug independent—reacts without presence of drugSensitized RBCs have shortened life span+ DAT

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Table 19-10 Summary of Classic Mechanisms of Drug-Induced Immune Hemolytic Anemia

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Alloimmune Hemolytic Anemia

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Alloimmune HAAb develops to a RBC Ag that the individual lacks. Individual exposed to transfused RBCs from another personAgs on transfused cells are lacking on RBCs of recipient.Stimulate production of Ab (alloAb)

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Alloimmune HAAb develops to a RBC Ag that the individual lacks.Abs react only with cells that possess the Ag.Not the individual's own RBC

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Alloimmune HAAb develops to a RBC Ag that the individual lacks.Detected by Ab screen (indirect AHg test)Seen in transfusion reactions and Hemolytic disease of the fetus or newborn (HDFN)

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Hemolytic Transfusion ReactionsResult of:Interaction of foreign (nonself) Ags on transfused RBCs and patient's plasma AbsImmunologic destruction of donor cells

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Hemolytic Transfusion ReactionsResult of:Two types of transfusion reactions Immediate (IgM)Occurring within 24 hr, intravascular hemolysisDelayed (IgG)Occurring 2–14 days after transfusion, extravascular hemolysis

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Table 19-11 Comparison of Acute and Delayed Hemolytic Transfusion Reactions

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Hemolytic Transfusion ReactionsTherapyAcuteTerminate transfusionSupportive careDelayedNo treatment

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Hemolytic Disease of the Fetus and Newborn (HDFN)Feto-maternal blood group incompatibilityMother forms alloantibodies against fetal RBC antigens.IgG antibodies cross placenta and destroy fetal RBCs in utero.

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Hemolytic Disease of the Fetus and Newborn (HDFN)Feto-maternal blood group incompatibilityThree categories:Rh(D) caused by anti-D (more severe disease)ABO caused by anti-A and/or anti-B (more common)“Other” caused by Abs to other blood group system Ags

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Table 19-12 Comparison of Hemolytic Disease of the Fetus and Newborn Caused by ABO and Rh(D)

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Hemolytic Disease of the Fetus and Newborn (HDFN)PathophysiologyFour conditions must be met for HDFN to occur:Mother must be sensitized to RBC Ag that she lacks.Fetus must possess Ag to which mother has been sensitized.Mother must produce Abs to foreign Ags.Mother's Ab must cross placenta, enter fetal circulation.

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Hemolytic Disease of the Fetus and Newborn (HDFN)Laboratory testingMotherABO and Rh typing, antibody screen (IAT)BabyABO and Rh typing, DAT (elution if necessary to identify Ab)

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Hemolytic Disease of the Fetus and Newborn (HDFN)Laboratory findingsBaby's peripheral blood: Macrocytic/normochromic, ↑ reticulocytes, leukocytosis with left shift, ↑ NRBCsRh HDFNMarked polychromasia, mild or absent poikilocytosis, few (if any) spherocytes, ↑ bilirubin, + DAT

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Hemolytic Disease of the Fetus and Newborn (HDFN)Laboratory findingsBaby's peripheral blood: ABO HDFNNRBCs, schistocytes, spherocytes, polychromasia, sl ↑ bilirubin, weakly + DAT

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Hemolytic Disease of the Fetus and Newborn (HDFN)TherapyPrevent hyperbilirubinemia and anemiaIntrauterine transfusionViability of fetus affectedPhototherapy (after birth) to reduce bilirubinExchange transfusion if bilirubin is rising> 1 mg/dL/hour or significant anemia

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Hemolytic Disease of the Fetus and Newborn (HDFN)Rh immune globulin (RhIG)Passive injection that contains anti-D that prevents maternal immunizationGiven at 28 weeks gestation and following birth of Rh+ infantDose determined on number of fetal cells in maternal circulationKleihauer-Betke TestRossette TestFlow cytometry

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Case Study—Chapter 19A 28-year-old female, Nancy, makes an appointment with her physician. She is tired all the time and short of breath with minor exertion.She indicates that the symptoms have been ongoing for about 3 weeks.She has no known history of chronic diseases.

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Case Study—Chapter 19Consider the initial laboratory tests that should be done to evaluate this patient's condition based on clinical history and symptoms.

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Case Study—Chapter 19Nancy's Initial CBCHb 7.0 g/dLHct 21%WBC count and platelet count are within the reference interval.Question 1:What are some reasons that she could have a low hemoglobin value?

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Case Study—Chapter 19When examining Nancy's peripheral blood smear, the laboratory professional noted:Presence of spherocytesReticulocytes count was elevated.

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Case Study—Chapter 19She called the blood bank and found that: The DAT was + with polyspecific AHG, anti-IgG, but negative with anticomplement

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Case Study—Chapter 19Question 2:What is the significance of the spherocytes?Question 3:Based on these results, what do you suspect is going on with this patient? Explain.

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Case Study—Chapter 19Two days later, Nancy's Hb dropped to 5.0 gm/dL.

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Case Study—Chapter 19The physician ordered several more tests.She had a positive IAT.The Ab reacted with all cells, including her own.Other test results indicated that this patient had systemic lupus erythematosus.

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Case Study—Chapter 19Question 4:What type of antibody appears to be present in this patient? Explain.Question 5:What is the relationship of the patient's primary disease, systemic lupus erythematosus, and her anemia?

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Case Study—Chapter 19The clinician wants to start Nancy's therapy and give her a transfusion.Question 6:How would knowing that Nancy had not been transfused in the last several months help you make a decision on the underlying cause of the antibody?

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Case Study—Chapter 19Question 7:What would you tell the clinician about giving a transfusion?Question 8:What kind of therapy can be used?